Esophageal eosinophilia occurs in patients with a number of disorders, including gastroesophageal reflux disease (GERD), Crohn disease, celiac disease, and eosinophilic esophagitis (EoE), a clinicopathologic chronic upper gastrointestinal tract disorder defined by esophageal dysfunction and eosinophil infiltration of 15 or more eosinophils per high-power field (hpf). Translational research in the past 10 years has uncovered a food allergen-driven, TH2 cell immune-mediated disease pathogenesis. Because GERD can also elicit esophageal eosinophilia, a consensus recommendation for the diagnosis of EoE requires a proton pump inhibitor (PPI) trial to exclude the possibility of acid-induced esophageal eosinophilia.
Although EoE is defined by a failed PPI trial, another form of esophageal eosinophilia that is frequently observed features tissue eosinophil levels as high as those in patients with EoE (in contrast to patients with GERD), diffuse infiltration along the esophageal length, and clinical characteristics representative of EoE, but PPI monotherapy is effective in reversing both histologic and clinical abnormalities. A number of explanations have been proposed, including (1) blockade of GERD-associated inflammation through the inhibition of acid by PPI; (2) the anti-inflammatory effects of PPI, such as inhibition of eotaxin-3 and signal transducer and activator of transcription; and (3) the interaction of acid and food allergens. Because of the lack of a clear understanding of the natural history and pathogenesis, this enigmatic condition is currently termed PPI-responsive esophageal eosinophilia (PPI-REE).
The frequency of PPI-REE among all patients with esophageal eosinophilia (>15 eosinophils/hpf) is substantial, ranging from 10% to 50%. Defining the underlying mechanisms of this inflammation in patients with PPI-REE will help to guide appropriate therapeutic strategies. However, to date, there have been no molecular, cellular, endoscopic, or clinical markers or pH test results that clearly distinguish these entities from one another. EoE is treated with topical corticosteroids and/or dietary elimination, whereas PPI-REE is treated, at least transiently, with acid suppression. Currently, it remains to be determined whether these 2 entities involve the same or different molecular pathogeneses. An understanding of their molecular similarities and differences would provide diagnostic and therapeutic clarity for practitioners and patients because both patients with PPI-REE and those with EoE are clinically similar in terms of clinical symptoms, endoscopic findings, male predominance, and high rate of atopy.